Clinical practice guidelines for cervical cancer: the Korean Society of Gynecologic Oncology guidelines.

This fifth revised version of the Korean Society of Gynecologic Oncology practice guidelines for the management of cervical cancer incorporates recent research findings and changes in treatment strategies based on version 4.0 released in 2020. Each key question was developed by focusing on recent notable insights and crucial contemporary issues in the field of cervical cancer. These questions were evaluated for their significance and impact on the current treatment and were finalized through voting by the development committee. The selected key questions were as follows: the efficacy and safety of immune checkpoint inhibitors as first- or second-line treatment for recurrent or metastatic cervical cancer; the oncologic safety of minimally invasive radical hysterectomy in early stage cervical cancer; the efficacy and safety of adjuvant systemic treatment after concurrent chemoradiotherapy in locally advanced cervical cancer; and the oncologic safety of sentinel lymph node mapping compared to pelvic lymph node dissection. The recommendations, directions, and strengths of this guideline were based on systematic reviews and meta-analyses, and were finally confirmed through public hearings and external reviews. In this study, we describe the revised practice guidelines for the management of cervical cancer.

In situ vaccination via tissue-targeted cDC1 expansion enhances the immunogenicity of chemoradiation and immunotherapy.

Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is a restriction on cytotoxic T cell immunity if DCs are not present in sufficient numbers in the tumor and draining lymph nodes to take up and present relevant cancer antigens. To address this bottleneck, we developed a therapeutic based on albumin fused with FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that demonstrated superior pharmacokinetic properties compared with Flt3L, including significantly longer half-life, accumulation in tumors and lymph nodes, and cross-presenting-DC expansion following a single injection. We demonstrated that Alb-Flt3L, in combination with standard-of-care chemotherapy and radiation therapy, serves as an in situ vaccination strategy capable of engendering polyclonal tumor neoantigen-specific immunity spontaneously. In addition, Alb-Flt3L-mediated tumor control synergized with immune checkpoint blockade delivered as anti-PD-L1. The mechanism of action of Alb-Flt3L treatment revealed a dependency on Batf3, type I IFNs, and plasmacytoid DCs. Finally, the ability of Alb-Flt3L to expand human DCs was explored in humanized mice. We observed significant expansion of human cross-presenting-DC subsets, supporting the notion that Alb-Flt3L could be used clinically to modulate human DC populations in future cancer therapeutic regimens.

Insights from molecular dynamics simulations of TRPV1 channel modulators in pain.

TRPV1 is a nonselective cation channel vital for detecting noxious stimuli (heat, acid, capsaicin). Its role in pain makes it a potential drug target for chronic pain management, migraines, and related disorders. This review updates molecular dynamics (MD) simulation studies on the TRPV1 channel, focusing on its gating mechanism, ligand-binding sites, and implications for drug design. The article also explores challenges in developing modulators, SAR optimization, and clinical trial studies. Efforts have been undertaken to concisely present MD simulation findings, with a focus on their relevance to drug discovery.

miR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.

The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells.

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

Efficacy and Safety of MED-01 Probiotics on Vaginal Health: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4-6 took MED-01 (5.0 × 109 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.

Comparison of Surgical Outcomes of Robotic versus Conventional Laparoscopic Hysterectomy of Large Uterus with Gynecologic Benign Disease.

Hysterectomy is commonly performed for benign gynecological diseases. Minimally invasive surgical approaches offer several advantages. Unfortunately, few studies have compared the outcomes of different types of minimally invasive surgeries. Therefore, this study aimed to compare the surgical outcomes of robotic hysterectomy (RH) and conventional laparoscopic hysterectomy (CLH) in benign gynecologic diseases. We performed a retrospective cohort study at a single center between January 2014 and July 2022. A total of 397 patients (RH: 197 and CLH: 200) who underwent minimally invasive hysterectomy for benign diseases with uterine size exceeding 250 g were enrolled, and factors related to the surgical outcomes were compared. The median age was 46 (range, 35-74) years, and the median uterine weight was 400 (range, 250-2720) g. There were no significant differences between the two groups regarding age, body mass index, uterine weight, hospital stay, estimated blood loss, or operating time. Intraoperative and postoperative complication rates were not significantly different between the two groups. RH was not inferior to CLH in terms of perioperative and immediate postoperative outcomes in our study.

Meta-Analysis of Survival Effects of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1).

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50−2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60−2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

Red blood cell indices as an effective marker for the existence and severity of endometriosis (STROBE).

To evaluate the association between red blood cell (RBC) indices (mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], MCH concentration [MCHC], red cell distribution width [RDW], hemoglobin [Hb], hematocrit [Hct], and neutrophil-to-lymphocyte ratio [NLR]) and the severity of endometriosis. Data were obtained from the medical records of 200 patients with endometriosis (stage I/II and stage III/IV groups), and 100 patients with benign ovarian tumors (control group), treated between September 2011 and April 2021. The mean Hb and Hct were significantly lower in the stage III/IV group compared to those in the control and stage I/II group (P = .015 and P = .004, respectively). The mean MCV, MCH, and Hb at postoperative day (POD)#1 were significantly lower in the stage III/IV group compared to those in the control and stage I/II group (P = .007, P = .032, and P < .0001, respectively). In addition, NLR at POD#1 was significantly higher in stage III/IV group compared to that in the control and stage I/II group. Multivariate analysis revealed that younger age (≤38 years old), lower preoperative MCV (≤88.5 fL), lower POD#1 Hb (<11.6g/dL), and higher POD#1 NLR (>2.5) were independent risk factors of stage III/IV endometriosis. Lower levels of RBC indices, including preoperative MCV and postoperative Hb, and higher postoperative NLR were significantly associated with the severity of endometriosis, which is potentially derived from a dysregulation in iron metabolism and inflammation.

YouTube as a source of information and education on endometriosis.

Many patients seek information online, including on social media, regarding various health topics. This study aimed to investigate whether YouTube videos on endometriosis could be a useful source for the general population, surgical trainees, and specialists. A YouTube search was conducted on December 26, 2021, using the search terms "endometriosis," "endometrioma," and "endometriotic cyst." Videos were sorted by view count, and the 100 videos with the highest view counts were chosen. After excluding 48 videos for various reasons, 52 were included in the final analysis. The number of views, duration, likes and dislikes, content type, and source of each video were recorded. We referred to a previous study to evaluate video quality. The 52 videos related to endometriosis had a total of 35,220,141 views (median 233,688, range 48,874-10,452,366). Based on authorship, the videos were categorized into videos uploaded by the medical group and the nonmedical group. The medical group mainly uploaded videos directly related to endometriosis, such as explanations or detailed surgical procedures for endometriosis (26/27, 96%), whereas the nonmedical group mainly uploaded videos about personal experiences and others (24/25, 96%; P <.001). Evaluating the score by each type of content, videos containing personal experiences (median score 6, range 3-10) scored significantly lower than videos containing other content such as explanations of the disease (median score 14, range 7-18; P < .001) and surgical procedures (median score 9, range 5-17; P < .001). Analysis according to the source, the number of views and video power index was significantly higher in the videos uploaded by the nonmedical group (P < .05). YouTube is currently not an appropriate source for patients to gain information on endometriosis. Credible videos with accurate information and clear, high-quality operative clips with proper scientific commentary should be uploaded by medical professionals and medical institutions to critically and rapidly appraise the quality of online video-disseminated information on endometriosis. In addition, advanced filtering using categories by YouTube's staff appears to be necessary.

Expression of antimicrobial peptides in the amniotic fluid of women with cervical insufficiency.

PROBLEM: Cervical insufficiency (CI) is associated with intra-amniotic infection or inflammation. Antimicrobial peptides (AMPs) in amniotic fluid may protect the fetus against microbial invasion, giving their broad-spectrum microbiocidal properties. We evaluated changes in amniotic fluid AMP expression in women with CI and assessed whether these changes are related to their pregnancy outcomes. METHOD OF STUDY: We evaluated amniotic fluid human neutrophil peptide 3 (HNP-3), human ß-defensin-2 (hBD-2), and LL-37 levels in 66 women with CI and 25 normal controls at 16-24 weeks of gestation. The CI group was divided into short cervix and cervical dilation groups, and the cervical dilation group was further divided into preterm and full-term delivery groups according to the pregnancy outcomes, and AMP expression was analyzed in each group. RESULTS: HNP-3 and hBD-2 levels were higher in women with CI than in normal controls and in the cervical dilation as compared to the short cervix group. Among women with cervical dilation, 22 delivered at full-term, and 23 had spontaneous preterm births. The hBD-2 level in amniotic fluid mid-pregnancy was higher in the full-term delivery than in the preterm delivery groups. However, LL-37 levels in amniotic fluid were low in women with CI and normal controls. CONCLUSIONS: Amniotic fluid HNP-3 and hBD-2 levels increased in women with CI compared with normal controls. Moreover, increased amniotic fluid hBD-2 levels mid-pregnancy were associated with favorable pregnancy outcomes in women with CI. AMPs in the amniotic fluid may participate in host defense against ascending infection in women with CI.

A Bayesian Network Meta-Analysis of First-Line Treatments for Non-Small Cell Lung Cancer with High Programmed Death Ligand-1 Expression.

We performed a Bayesian network meta-analysis (NMA) to suggest frontline treatments for advanced non-small cell lung cancer (NSCLC) showing high programmed death ligand-1 (PD-L1) expression. A total of 5237 patients from 22 studies were included. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference in survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for advanced NSCLC with high PD-L1 expression. However, considering that there was no significant difference in survival outcomes among treatment regimens incorporating immunotherapy and that ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression.

Automated Diagnosis of Cervical Intraepithelial Neoplasia in Histology Images via Deep Learning.

Artificial intelligence has enabled the automated diagnosis of several cancer types. We aimed to develop and validate deep learning models that automatically classify cervical intraepithelial neoplasia (CIN) based on histological images. Microscopic images of CIN3, CIN2, CIN1, and non-neoplasm were obtained. The performances of two pre-trained convolutional neural network (CNN) models adopting DenseNet-161 and EfficientNet-B7 architectures were evaluated and compared with those of pathologists. The dataset comprised 1106 images from 588 patients; images of 10% of patients were included in the test dataset. The mean accuracies for the four-class classification were 88.5% (95% confidence interval [CI], 86.3-90.6%) by DenseNet-161 and 89.5% (95% CI, 83.3-95.7%) by EfficientNet-B7, which were similar to human performance (93.2% and 89.7%). The mean per-class area under the receiver operating characteristic curve values by EfficientNet-B7 were 0.996, 0.990, 0.971, and 0.956 in the non-neoplasm, CIN3, CIN1, and CIN2 groups, respectively. The class activation map detected the diagnostic area for CIN lesions. In the three-class classification of CIN2 and CIN3 as one group, the mean accuracies of DenseNet-161 and EfficientNet-B7 increased to 91.4% (95% CI, 88.8-94.0%), and 92.6% (95% CI, 90.4-94.9%), respectively. CNN-based deep learning is a promising tool for diagnosing CIN lesions on digital histological images.

Prognostic value of protein tyrosine kinase 6 overexpression in cancers: a meta-analysis.

BACKGROUND: Protein tyrosine kinase 6 (PTK6) plays an important role in cell proliferation and differentiation. However, the functions of PTK6 appear highly context-dependent and differ depending on the cell type, as well as its intracellular localization. High PTK6 expression in tumor has been associated with poor pathological features and prognosis in some studies, but other studies have reported opposite results. Therefore, we performed this meta-analysis to derive more precise estimations of the association of PTK6 expression with prognosis and clinicopathological features in cancer patients. METHODS: We conducted a literature search in PubMed, Ovid MEDLINE, and MEDLINE databases to cover all articles published until June 2021. All 1475 patients from the eight studies were included in the meta-analysis. Because of heterogeneity in PTK6 expression in non-tumor tissues, the included studies were divided into two subgroups according to PTK expression in non-tumor tissues: the low expression subgroup (LESG) or high expression subgroup (HESG). RESULTS: Patients with high PTK expression showed significantly worse overall survival (OS) in LESG (Hazard Ratio (HR) = 2.53 [95% Confidence Interval (CI), 1.68-3.83], p < 0.0001), but significantly better OS in HESG (HR = 0.56 [95% CI, 0.40-0.78], p = 0.0006). PTK6 expression also showed different associations with clinicopathological features, such as advanced T classification, stage, and differentiation according to PTK6 expression in non-tumor tissues. CONCLUSIONS: PTK6 expression in tumor was a prognostic factor in patients with various cancers, but the direction of prognosis differs, depending on the degree of PTK6 expression in non-tumor tissues.

FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis.

The fibroblast growth factor-4 receptor (FGFR4) is a member of receptor tyrosine kinase. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor has been shown to increase genetic susceptibility to cancers. However, its prognostic impact in cancer patients still remains controversial. Herein, we performed this meta-analysis to evaluate the clinicopathological and prognostic impacts of the FGFR4 Gly388Arg polymorphism in patients with cancer. We carried out a computerized extensive search using PubMed, Medline, and Ovid Medline databases up to July 2021. From 44 studies, 11,574 patients were included in the current meta-analysis. Regardless of the genetic models, there was no significant correlation of the FGFR4 Gly388Arg polymorphism with disease stage 3/4. In the homozygous model (Arg/Arg vs. Gly/Gly), the Arg/Arg genotype tended to show higher rate of lymph node metastasis compared with the Gly/Gly genotype (odds ratio = 1.21, 95% confidence interval (CI): 0.99-1.49, p = 0.06). Compared to patients with the Arg/Gly or Arg/Arg genotype, those with the Gly/Gly genotype had significantly better overall survival (hazard ratios (HR) = 1.19, 95% CI: 1.05-1.35, p = 0.006) and disease-free survival (HR = 1.25, 95% CI: 1.03-1.53, p = 0.02). In conclusion, this meta-analysis showed that the FGFR4 Gly388Arg polymorphism was significantly associated with worse prognosis in cancer patients. Our results suggest that this polymorphism may be a valuable genetic marker to identify patients at higher risk of recurrence or mortality.

Anti-Mullerian Hormone Changes Following Laparoscopic Ovarian Cystectomy: A Prospective Comparative Study.

PURPOSE: To investigate whether laparoscopic ovarian cystectomy (LOC) affects ovarian reserve. PATIENTS AND METHODS: In 46 premenopausal women, who underwent either LOC (study group, n=26) or laparoscopic myomectomy (LM) (control group, n=20), serum anti-Mullerian hormone (AMH) levels were measured pre-operatively (AMH0), and postoperatively at 7 days (AMH1), 2 months (AMH2), and 6 months (AMH3). Changes in AMH from baseline level (AMH0) in each group were compared. RESULTS: AMH0 did not differ between the two groups (3.5 ± 3.33 in LOC vs 2.4 ± 2.72 in LM, P=0.250). AMH1, AMH2, and AMH3 in each group were also similar. However, a significant decline of AMH (ie more than 50% decrease compared to AMH0) at postoperative 6 months occurred more frequently in the LOC group than in the LM group. In the sub-analysis of the LOC group, a significant decline of AMH at postoperative 2 months and 6 months was highly correlated with bilateral ovarian tumors (P=0.001). CONCLUSION: Compared to LM, serum AMH level showed a minimal decrease after 1 week following LOC, which did not revert to normal over 6 months of follow-up. In addition, a significant decline of ovarian reserve at postoperative 6 months was significantly more frequent in the LOC group, suggesting that LOC may have more adverse effects on ovarian reserve compared to the LM (control) group. Thus, care is required during the LOC procedure, specifically in women with bilateral tumors.

Content Analysis and Quality Evaluation of Cesarean Delivery-Related Videos on YouTube: Cross-sectional Study.

BACKGROUND: YouTube is one of the most popular open-access video-sharing websites, and it is also used to obtain health care information. Cesarean delivery is the most common major surgical intervention in many countries. Videos related to cesarean delivery have also been uploaded to YouTube. However, no study has explored the overall quality of cesarean delivery videos on the platform. OBJECTIVE: The objective of this study was to analyze the content and evaluate the quality of the most frequently viewed videos related to cesarean delivery that are accessible on YouTube. METHODS: We searched for a total of 18 terms by combining the 6 terms retrieved from Google AdWords and the 3 terms c section, cesarean section, and cesarean delivery, which are used interchangeably. Videos were sorted by view count, and the 100 videos with the highest view counts were chosen. The number of views, duration, likes and dislikes, content type, and source of each video were recorded. In evaluating the quality of the videos, we referred to a previous study. Additionally, we developed a detailed scoring method that comprehensively evaluates the videos related to cesarean delivery by including the necessary information for each element of the cesarean delivery and whether scientific evidence was presented. RESULTS: Of the 100 videos analyzed, the most prevalent content (n=28) was videos that contained the actual surgical procedure of a cesarean delivery, and the most common source of cesarean delivery videos was physicians (n=30). Videos directly related to cesarean delivery, such as explanation of the surgery and the actual surgical procedure, were mainly uploaded by medical groups and scored higher than the videos indirectly related to cesarean delivery, which were mainly uploaded by nonmedical groups. In addition, videos directly related to cesarean delivery were more often uploaded earlier in time, with lower like ratios compared to indirect videos. CONCLUSIONS: YouTube is currently not an appropriate source for patients seeking information on cesarean delivery.

Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study.

BACKGROUND: The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls. METHODS: RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA. RESULTS: Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group. CONCLUSIONS: Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.

Classification of cervical neoplasms on colposcopic photography using deep learning.

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.